Structure/activity relations of N-methyl-D-aspartate receptor ligands as studied by their inhibition of [3H]D-2-amino-5-phosphonopentanoic acid binding in rat brain membranes

Neuroscience. 1988 Jul;26(1):17-31. doi: 10.1016/0306-4522(88)90124-8.


Structure/activity relations of agonists and antagonists for the N-methyl-D-aspartate receptor have been investigated by measuring the ability of a large range of substances to inhibit binding of [3H]2-amino-5-phosphonopentanoate to rat brain membranes. A major difference between optimum structures for agonist and antagonist activity lay in the differential effectiveness of sulphonic and phosphonic acid groups as the omega-acidic terminal in these two types of compound. The sulphonic acid moiety was an effective omega-acidic terminal in short chain agonists, but not in longer chain antagonists, while the phosphonic acid group was the most effective omega-acidic terminal in longer chain antagonists, but was only very weakly active in short chain agonists. It is proposed that the binding site of the omega-acidic terminal of antagonists is different from that for the omega-acidic group of agonists. Other structural features conducive to effective interaction of ligands with the receptor are discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Amino-5-phosphonovalerate
  • Amino Acids / metabolism*
  • Animals
  • Binding, Competitive
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism*
  • Kinetics
  • Molecular Conformation
  • Rats
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Neurotransmitter / drug effects
  • Receptors, Neurotransmitter / metabolism*
  • Structure-Activity Relationship
  • Subcellular Fractions / metabolism
  • Valine / analogs & derivatives*
  • Valine / metabolism


  • Amino Acids
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Neurotransmitter
  • 2-Amino-5-phosphonovalerate
  • Valine